Oxygen Partition Between Microvessels and Tissue: Significance for the Design of Blood Substitutes

Summary

Correction of blood losses with blood substitutes alter the pO₂ distribution in the microcirculation, with outcomes depending on the final viscosity of the circulating blood and the vasoactivity induced to the restore normal distribution of pO₂. Vasoactivity has an oxygen cost shown by the oxygen consumption of the arteriolar microcirculation. Vasodilators lower arteriolar oxygen consumption delivering more oxygen to the tissues, and vice versa. Increased oxygen delivery to the arterioles by right shifted oxygen dissociation causes autoregulatory vasoconstriction, a problem aggravated by low blood and plasma viscosity that lowers NO endothelial NO production. Restoration of tissue function is achieved when no portion of the tissue falls below the threshold of anaerobic metabolism. This goal is attained by using high affinity modified hemoglobins that act as a reservoir of oxygen only deployed when the circulating blood arrives at tissue regions where pO₂ is very low. Given these premises, restoration of tissue function after severe blood losses requires the re-establishment of oxygen delivery capacity and pO₂ distribution. This is attained by tailoring blood and plasma viscosity and oxygen dissociation properties to insure that no portion of the tissue lacks oxygen delivery, even though overall tissue pO₂ may be abnormally low.